DESCRIPTION: This is a competitive renewal request for continuation of a program of studies aimed at understanding the chemical principals governing the folding, stability and self-association of beta-sheet structures in aqueous solution. Three lines of investigation are proposed: 1) the design and synthesis of templates that can be inserted into sequences to facilitate sheet formation and to determine of what kind of amino acids are thermodynamically favored to form sheets, and the role of hydrophobic clusters and hydrogen bonds in driving sheet formation; 2) studies of a naturally occurring 38-residue, 3-stranded antiparallel beta-sheet domain (termed the WW domain because of its 2 Trp residues) aimed at understanding the interactions that stabilize the domain structure; 3) studies of intermolecular beta-sheet formation using hosts that can selectively bind peptides. The peptides are obtained by solid phase chemical synthesis, and in the case of the WW domain, using a bacterial expression system. The peptide structures are evaluated by analytical ultracentrifugation, CD, FTIR, NMR, mass spectroscopy, binding of hydrophobic probes (ANS), fluorescence, as well as sequence analysis, in the case of the WW domain motif that has been identified in a number of proteins.